WIN 55,212-2

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WIN 55,212-2
Legal status
Legal status
Identifiers
  • (11R)-2-methyl-11-[(morpholin-4-yl)methyl]-3-(naphthalene-1-carbonyl)-9-oxa-1-azatricyclo[6.3.1.0⁴,¹²]dodeca-2,4(12),5,7-tetraene
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC27H26N2O3
Molar mass426.52 g/mol g·mol−1
3D model (JSmol)
  • CC1=C(C2=C3N1[C@@H](COC3=CC=C2)CN4CCOCC4)C(=O)C5=CC=CC6=CC=CC=C65
  • InChI=1S/C27H26N2O3/c1-18-25(27(30)22-9-4-7-19-6-2-3-8-21(19)22)23-10-5-11-24-26(23)29(18)20(17-32-24)16-28-12-14-31-15-13-28/h2-11,20H,12-17H2,1H3/t20-/m1/s1 ☒N
  • Key:HQVHOQAKMCMIIM-HXUWFJFHSA-N ☒N
 ☒NcheckY (what is this?)  (verify)
Pancreatic stellate cells. The cells in the lower frame are under the action of WIN 55,212-2. They are thought to assume a more "quiescent" phenotype. From Michalski et al., 2008.[1]

WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure.[2][3][4]

WIN 55,212-2 is a potent cannabinoid receptor agonist[5] that has been found to be a potent analgesic[6] in a rat model of neuropathic pain.[7] It activates p42 and p44 MAP kinase via receptor-mediated signaling.[8]

At 5 µM WIN 55,212-2 inhibit ATP production in sperm in a CB1 receptor-dependent fashion.[9]

WIN 55,212-2, along with HU-210 and JWH-133, may prevent the inflammation caused by amyloid beta proteins involved in Alzheimer's disease, in addition to preventing cognitive impairment and loss of neuronal markers. This anti-inflammatory action is induced through agonist action at cannabinoid receptors, which prevents microglial activation that elicits the inflammation. Additionally, cannabinoids completely abolish neurotoxicity related to microglial activation in rat models.[citation needed] WIN 55,212-2 impairs memory and brain network functional connectivity in mice.[10]

WIN 55,212-2 is a full agonist at the CB1 cannabinoid receptor (Ki = 1.9 nM) and has much higher affinity than THC (Ki = 41 nM) for this receptor.[11] WIN 55,212-2 is also an agonist of the PPARα and PPARγ nuclear receptors.[12]

WIN 55,212-2 reduces voluntary wheel running in laboratory mice, but with effects that depend on both genetic background and sex.[13]

WIN 55,212-2 is illegal in the UK.[14]

See also

References

  1. ^ Michalski, C.; et al. (2008). Gluud, Christian (ed.). "Cannabinoids Reduce Markers of Inflammation and Fibrosis in Pancreatic Stellate Cells". PLoS ONE. 3 (2): e1701. Bibcode:2008PLoSO...3.1701M. doi:10.1371/journal.pone.0001701. PMC 2253501. PMID 18301776.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  2. ^ Compton, DR; et al. (1992). "Aminoalkylindole Analogs: Cannabimimetic Activity of a Class of Compounds Structurally Distinct from Δ9-Tetrahydrocannabinol". Journal of Pharmacology and Experimental Therapeutics. 263 (3): 1118–1126.
  3. ^ Ferraro, L.; Tomasini, M. C.; Gessa, G. L.; Bebe, B. W.; Tanganelli, S.; Antonelli, T. (2001). "The Cannabinoid Receptor Agonist WIN 55,212-2 Regulates Glutamate Transmission in Rat Cerebral Cortex: An in Vivo and in Vitro Study". Cerebral Cortex. 11 (8): 728–733. doi:10.1093/cercor/11.8.728. PMID 11459762.
  4. ^ Zhang, Q.; et al. (2002). "In vitro metabolism of R(+)-2,3-dihydro-5-methyl-3-(morpholinyl)methylpyrrolo 1,2,3-de1,4-benzoxazinyl-(1-naphthalenyl) methanone mesylate, a cannabinoid receptor agonist". Drug Metabolism and Disposition. 30 (10): 1077–1086. doi:10.1124/dmd.30.10.1077. PMID 12228183.
  5. ^ Felder, C. C.; Joyce, K. E.; Briley, E. M.; Mansouri, J.; MacKie, K.; Blond, O.; Lai, Y.; Ma, A. L.; Mitchell, R. L. (1995). "Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors". Molecular Pharmacology. 48 (3): 443–450. PMID 7565624.
  6. ^ Meng, I. D.; Manning, B. H.; Martin, W. J.; Fields, H. L. (1998). "An analgesia circuit activated by cannabinoids". Nature. 395 (6700): 381–383. Bibcode:1998Natur.395..381M. doi:10.1038/26481. PMID 9759727.
  7. ^ Herzberg, U.; Eliav, E.; Bennett, G. J.; Kopin, I. J. (1997). "The analgesic effects of R(+)-WIN 55,212–2 mesylate, a high affinity cannabinoid agonist, in a rat model of neuropathic pain". Neuroscience Letters. 221 (2–3): 157–160. doi:10.1016/S0304-3940(96)13308-5. PMID 9121688.
  8. ^ Bouaboula, M.; Poinot-Chazel, C.; Bourrié, B.; Canat, X.; Calandra, B.; Rinaldi-Carmona, M.; Le Fur, G.; Casellas, P. (1995). "Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1". The Biochemical Journal. 312 (Pt 2): 637–641. doi:10.1042/bj3120637. PMC 1136308. PMID 8526880.
  9. ^ Morgan, D. J.; Muller, C. H.; Murataeva, N. A.; Davis, B. J.; MacKie, K. (2012). "Δ9-Tetrahydrocannabinol (Δ9-THC) attenuates mouse sperm motility and male fecundity". British Journal of Pharmacology. 165 (8): 2575–2583. doi:10.1111/j.1476-5381.2011.01506.x. PMC 3423255. PMID 21615727.
  10. ^ Mouro, Francisco M; Ribeiro, Joaquim A; Sebastião, Ana M; Dawson, Neil (10 July 2018). "Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity". Journal of Neurochemistry. doi:10.1111/jnc.14549. PMID 29989183.
  11. ^ Kuster, J. E.; et al. (1993). "Aminoalkylindole binding in rat cerebellum: selective displacement by natural and synthetic cannabinoids". The Journal of Pharmacology and Experimental Therapeutics. 264 (3): 1352–1363. PMID 8450470.
  12. ^ O'Sullivan SE (2016). "An update on PPAR activation by cannabinoids". Br J Pharmacol. 173 (12): 1899–910. doi:10.1111/bph.13497. PMC 4882496. PMID 27077495.
  13. ^ Keeney BK, et al. (2012). "Sex differences in cannabinoid receptor-1 (CB1) pharmacology in mice selectively bred for high voluntary wheel-running behavior". Pharmacology Biochemistry and Behavior. 101 (4): 528–537. doi:10.1016/j.pbb.2012.02.017. PMID 22405775.
  14. ^ "The Misuse of Drugs Act 1971 (Amendment) Order 2013".

External links

  • Enzo Life Sciences Win 55,212-2 Data Sheet
  • The cannabinoid WIN 55,212-2 inhibits transient receptor potential vanilloid 1 (TRPV1) and evokes peripheral antihyperalgesia via calcineurin. 2006 Jul 18; PMID 16849427
  • JNeurosci.org Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation
  • New Scientist: Hope for cannabis-based drug for Alzheimer's
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